History of MDMA

MDMA, commonly known by its street names “Ecstasy” or “Molly,” is a psychoactive drug that has a rich, yet tumultuous history. It is renowned for its use in recreational settings, therapy, and the controversy surrounding its legal status.

The story of MDMA begins in 1912 when the German pharmaceutical company Merck first synthesized the drug. It was originally developed as an intermediate chemical to create medications that control bleeding. At this point, Merck was not interested in MDMA’s psychoactive properties, and the compound remained mostly dormant for several decades.

The reemergence of MDMA can be traced to the 1960s and 1970s, which was an era marked by a surge in the exploration of consciousness and psychoactive substances. During this period, Dr. Alexander Shulgin, an American chemist and psychopharmacologist, rediscovered MDMA. After synthesizing it, he tried the compound himself and was intrigued by its effects. Shulgin believed that the empathogenic properties of the drug, which made people feel deeply connected with themselves and others, could be invaluable in psychotherapy. Through his tireless advocacy, MDMA found its way into the hands of psychotherapists across the United States.

Early Therapeutic Use

In the late 1970s and early 1980s, MDMA was used legally and often informally referred to as “Adam” within the therapeutic community. The therapists who used it reported that it enabled patients to open up and discuss painful or traumatic experiences with ease. The drug was seen as an adjunct to psychotherapy, helping patients to make breakthroughs in cases where traditional therapeutic approaches were ineffective.

This early supplemental role of MDMA as a tool used by psychotherapists set the stage for the compound’s resurgence in later years.

Early Recreational Use

However, during the early 1980s, MDMA also gained popularity as a recreational drug. It became synonymous with the burgeoning rave culture, where people would gather in clubs and dance to electronic music. The drug’s energizing and euphoric effects made it a perfect fit for these all-night dance parties. As the drug gained popularity in the club scene, it earned the street name “Ecstasy”.

This sudden surge in recreational use caught the attention of media and lawmakers. The U.S. Drug Enforcement Administration (DEA) grew concerned about the drug’s safety and potential for abuse. In 1985, despite protests from the medical community and users who attested to the benefits of MDMA, the DEA classified it as a Schedule I substance. This category is reserved for substances that are deemed to have a high potential for abuse and no accepted medical use. The classification effectively put an end to the therapeutic use of MDMA in the United States and severely limited scientific research into its potential benefits.

Despite the legal restrictions, recreational use continued and spread globally. Ecstasy became an integral part of the rave and electronic dance music cultures of the 1990s and early 2000s. However, this period also saw a rise in concerns regarding the purity and safety of the drug. Pills sold as Ecstasy often contained other substances, sometimes more dangerous than MDMA itself, leading to health risks and fatalities.

The Psychedelic Revolution

In the mid-2000s, there was a resurgence in interest regarding the therapeutic potential of MDMA, particularly for the treatment of post-traumatic stress disorder (PTSD). Organizations such as the Multidisciplinary Association for Psychedelic Studies (MAPS) began to push for clinical trials to investigate the efficacy of MDMA-assisted psychotherapy. These studies have shown promising results, with many participants experiencing significant reductions in PTSD symptoms.

As we approach the present day, MDMA is at a critical juncture in its history. On one hand, it remains a popular recreational drug associated with dance music culture. On the other hand, it is gaining legitimacy as a powerful therapeutic tool. The FDA in the United States has granted MDMA “breakthrough therapy” designation for the treatment of PTSD, and it is expected to exit Phase 3 clinical trials soon.

What does MDMA feel like?

MDMA induces altered sensations, increased energy, empathy, and pleasure. However, everyone’s experience with MDMA can vary depending on a variety of factors, including dose, the individual’s mental and physical health, and the environment in which it is taken. 

The Come-up & Experience

Approximately 30 to 45 minutes after taking MDMA, users typically begin to experience its effects. The initial sensations can include feeling euphoric and energized. Users often report a heightened sense of well-being, increased sociability, and feelings of mental clarity.

One of the most characteristic effects of MDMA is an enhanced sense of empathy and emotional closeness. This effect is one of the primary reasons it is used in psychotherapy. Users may feel a strong connection to those around them, experience increased compassion, and find it easier to discuss emotions and personal issues.

Physically, MDMA can also cause heightened sensory perception. Sounds may seem richer, colors more vibrant, and touch more pleasurable. This heightened sensory perception is one reason why the drug is popular in settings with music and dancing, such as clubs or music festivals.

How MDMA Works On Your Brain

MDMA primarily works by increasing the activity of three neurotransmitters in the brain: serotonin, dopamine, and norepinephrine.

Serotonin: MDMA induces a massive release of serotonin, a neurotransmitter that plays a key role in the regulation of mood, sleep, pain, and appetite. Serotonin also triggers the release of the hormones oxytocin and vasopressin, which play roles in love, trust, sexual arousal, and other social experiences. This flood of serotonin is primarily responsible for the euphoric and empathetic feelings users experience during the first few hours after taking MDMA.

Dopamine: This neurotransmitter is associated with reward and pleasure. MDMA increases the levels of dopamine in the brain, contributing to the drug’s stimulant effects, such as increased energy and activity.

Norepinephrine: Also known as noradrenaline, norepinephrine increases heart rate and blood pressure, which are typical physiological responses to MDMA use.

MDMA acts by entering neurons via the same transporter proteins that these neurotransmitters use to re-enter cells after they’ve been released into the synapse (the space between neurons). Once inside the neuron, MDMA inhibits the vesicular transporters, causing neurotransmitters to be released from their storage sites into the synapse, resulting in increased neurotransmitter levels.

A crucial aspect of MDMA’s mechanism is its effect on the serotonin transporter (SERT). MDMA binds to SERT and reversibly inhibits its function, but it also causes SERT to work in reverse — moving serotonin out of the neuron and into the synapse. This massive increase in synaptic serotonin levels triggers the cascade of effects associated with MDMA. Imagine your neurons are like sponges for serotonin, and once the serotonin has been absorbed by the sponge, it can no longer be used. MDMA squeezes the sponge out, thereby adding more serotonin into your system. This is what is meant by “cascade” of effects.

The Come-down

Depending on the quality of MDMA you use and the circumstances in which you use it, you will have varying levels of side effects after your experience comes to an end. Generally speaking, when you ingest pure MDMA and do not mix it with alcohol or any other psychoactive substances, there is a higher likelihood of a “halo” effect, which is a subtle sense of euphoria in the 24-48 hours after your experience.

If, on the other hand, you mix MDMA with other psychoactive substances, such as alcohol, or you are in an uncomfortable environment during your experience, there is a higher likelihood that you will experience negative mood effects, often called the “comedown” or “crash,” in the days following use.

After MDMA use, there’s typically a period of neurotransmitter depletion, when serotonin levels are particularly low. The experience itself is very taxing on your body’s energy levels as well, so you may find that you have lower energy levels than normal in the days that follow the experience. These effects will dissipate within 48-72 hours.

Negative comedown effects are maximized with higher doses and when the ingested MDMA has been mixed with other compounds (such as is the case with most pressed pills bought in clubs). In therapeutic settings with “clean” MDMA in crystal form, proper dosage, and the proper environmental controls in place, such as the right set and setting, these comedown effects are minimized and often avoided entirely.

It’s important to note that MDMA can also have negative effects. Some people may experience nausea, chills, sweating, involuntary teeth clenching, muscle cramping, blurred vision, and, in some cases, disorientation or panic attacks. This is why it is of the utmost importance to pursue MDMA therapy with a professional facilitator who has lots of experience leading people through MDMA therapy.

Supplementation

MDMA is taxing on the body, which means it’s important to supply your body with supplemental vitamins to aid in neuroprotection and the replenishment of important nutrients. The list below contains an effective supplementation protocol for pre-, during, and post-MDMA therapy sessions.

Pre-Session

Alpha Lipoic Acid (1200 mg) and Acetyl L-Carnitine (500mg) as neuroprotective antioxidants

Vitamin C (1,000 mg) as an antioxidant

Magnesium Glycinate (840 mg) to relieve jaw clenching and cramping

Ginger (7700 mg) to relieve gastrointestinal distress in cases of oral MDMA ingestion

During Session

Charcoal can be used within 20-30 minutes of ingestion in case of overdose

(Redose) Alpha Lipoic Acid (1200 mg) and Acetyl L-Carnitine (500mg) as neuroprotective antioxidants

(Redose) Vitamin C (1,000 mg) as an antioxidant

(Redose) Magnesium Glycinate (840 mg) to relieve jaw clenching and cramping

Post-Session & 3 Days After (Once Daily)

Alpha Lipoic Acid (1200 mg) as a neuroprotective antioxidant (also helps with sleep post-MDMA)

L-Tryptophan (500 mg), SAMe (400mg), and 5-HTP (400 mg) as building blocks for serotonin production

(As needed) Magnesium Glycinate (840 mg) to relieve jaw clenching and cramping

Common Complications

SSRI Antidepressants

SSRIs are a type of prescription antidepressant that have been prescribed to those suffering from depression and anxiety. Although MDMA has been shown to permanently alleviate depression and anxiety symptoms in test subjects, those who are on SSRI medication are in a specific category that requires special treatment.

SSRIs function by inhibiting the reuptake of serotonin, a neurotransmitter associated with mood regulation, leading to increased serotonin levels in the brain. This mechanism helps alleviate symptoms of depression and anxiety. Conversely, MDMA acts primarily by increasing the release of serotonin, dopamine, and norepinephrine, resulting in enhanced mood and heightened sensory perception.

The biggest concern when combining SSRIs and MDMA is the triggering of serotonin syndrome, a potentially life-threatening condition characterized by excessive serotonin levels in the brain. Symptoms may include agitation, confusion, rapid heartbeat, high blood pressure, dilated pupils, and in severe cases, seizures or organ failure.

Although serotonin syndrome typically requires very, very high levels of MDMA use, usually repeated in a short period of time, in order to be activated, it is nonetheless a concern due to the fact that SSRIs have a blunting effect on MDMA, leading unsuspecting users to overdose on MDMA, thus triggering the syndrome.

It is of the utmost importance to work with a professional facilitator for your MDMA therapy if you are, or have recently come off of, SSRI antidepressants. They will help you begin a weaning-off period in order to best prepare for an MDMA therapy session.

MAOI Antidepressants

MAOIs work by inhibiting the action of the enzyme monoamine oxidase, which breaks down neurotransmitters like serotonin, dopamine, and norepinephrine. This inhibition increases the levels of these neurotransmitters in the brain, alleviating symptoms of depression.

While MAOIs have the same concerns related to serotonin syndrome as SSRIs, the risks are slightly higher. MAOIs are a first-generation antidepressant while SSRIs are a second-generation compound, which means MAOIs are less common nowadays; however, they are still around.

An additional risk when combining MAOIs with MDMA is hypertension. MAOIs can interact with substances that contain tyramine, a compound found in many foods and beverages. When tyramine is ingested, it can cause a sudden increase in blood pressure. MDMA can also raise blood pressure and heart rate. Combining MAOIs and MDMA can lead to a dangerous hypertensive crisis, potentially resulting in stroke, heart attack, or other cardiovascular complications.

As with SSRIs, it’s important to work with a professional who can properly gauge your specific situation and your body’s expected tolerance, and potential negative interactions, with MDMA.